MDA - Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)http://mda.org/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease
enResearch Briefs: FA, MG, MM, MMD1, gene therapyhttp://mda.org/quest/research-briefs-fa-mg-mm-mmd1-gene-therapy
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><h4 class="article-subhead">Edison drugs target FA, mitochondrial diseases</h4>
<p><a href="http://www.edisonpharma.com/" target="_blank">Edison Pharmaceuticals</a>, a biotechnology company, announced in June 2011 that its experimental drug <em>EPI-A0001</em> has shown promise in a 28-day, placebo-controlled trial in people with <strong><a href="http://www.mda.org/disease/fa.html" target="_blank">Friedreich's ataxia (FA)</a></strong>. (See <a href="http://www.edisonpharma.com/PressReleases/110610_Edison%20Pharmaceuticals%20announces%20results%20of%20EPI-A0001%20phase%202A%20double%20blind%20placebo%20controlled%2028-day%20clinical%20trial%20in%20the%20mitochondrial%20disease%20Friedreich%27s%20ataxia.pdf" target="_blank">Edison Pharmaceuticals Announces Results of EPI-A001 Phase 2A Double-Blind, Placebo-Controlled 28-Day Clinical Trial</a>.)</p>
<p>In this phase 2a trial, there was improvement in the Friedreich's Ataxia Rating Scale scores in those taking the low and high dose of EPI-A0001 in comparison to those taking a placebo.</p>
<p>The company also announced in June that its experimental drug EPI-743, designed to treat <a href="http://www.mda.org/disease/mito.html" target="_blank">mitochondrial diseases</a>, is available for certain patients with these diseases in a special "expanded access" program. (See <a href="http://www.edisonpharma.com/PressReleases/110608_Edison%20Pharmaceuticals%20to%20provide%20expanded%20access%20to%20EPI-743%20for%20mitochondrial%20disease.pdf" target="_blank">Edison Pharmaceuticals to Provide Expanded Access to EPI-743 for Mitochondrial Disease</a>.)</p>
<p>Edison is also studying EPI-743 in a clinical trial in mitochondrial diseases. (See <a href="http://www.clinicaltrials.gov/ct2/show/NCT01370447" target="_blank">EPI-743 for Mitochondrial Respiratory Chain Diseases</a>; or search for trial NCT01370447 on <a href="http://clinicaltrials.gov/" target="_blank">clinicaltrials.gov</a>.)</p>
<p>Edison's products are designed to improve the function of <em>mitochondria</em>, the energy-producing parts of cells. Mitochondria are affected in a number of diseases, including FA.</p>
<h4 class="article-subhead">IVIG, plasmapheresis equally effective in adults with MG</h4>
<p>A 28-day study of 84 adults with moderate to severe <strong><a href="http://www.mda.org/disease/mg.html" target="_blank">myasthenia gravis (MG)</a></strong>who were randomly assigned to receive <em>intravenous immunoglobulins (IVIG)</em> or <em>plasmapheresis</em> (also called <em>plasma exchange</em>) has found that the treatments are equally effective, that both are well-tolerated, and that the duration of benefit is about the same.</p>
<p>The study, published June 7, 2011, in Neurology, noted that people with MG who have more severe weakness and antibodies to <em>acetylcholine receptors</em> may respond better to these treatments than other patients. (See <a href="http://www.neurology.org/content/76/23/2017.abstract" target="_blank">Comparison of IVIg and PLEX in patients with myasthenia gravis</a>.)</p>
<p>Acetylcholine receptors, located at the junction of nerve and muscle fibers, are the targets of immune-system attack in many people with MG. IVIG and plasmapheresis are procedures designed to modify the immune response, as are several medications used to treat MG.</p>
<h4 class="article-subhead">New lead found in search for MMD1 (DM1) treatment</h4>
<p>MDA grantee Ruben Artero at the University of Valencia in Spain was part of a research group that recently identified a new way to block a disease-causing genetic mutation underlying<strong><a href="http://www.mda.org/disease/dm.html" target="_blank">type 1 myotonic dystrophy (MMD1, or DM1)</a></strong>.</p>
<p>The experiments were conducted in a fly model of the disease, but the researchers say that the blocking molecule they've identified, called <em>ABP1</em>, "represents a promising approach in the generation of new effective treatments for DM1."</p>
<p>The scientific paper was published online July 5, 2011, in Proceedings of the American Academy of Sciences. (See <a href="http://www.pnas.org/content/early/2011/06/27/1018213108.abstract" target="_blank">In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models</a>.)</p>
<p>See also <a href="http://quest.mda.org/news/disrupted-disease-process" target="_self">Disrupted Disease Process</a> for a related article about a potentially therapeutic molecule identified in 2009 in a mouse model of MMD1.</p>
<h4 class="article-subhead">'Genome editing' seen as next step for gene therapy</h4>
<p>A new type of gene therapy that precisely "edits" genetic information like a word-processing program, inserting functional DNA and removing nonfunctional DNA at a precise location, has successfully treated the blood-clotting disorder <em>hemophilia</em> in a mouse model of this disease. The new approach may prove safer and more effective than those now in use as gene therapy strategies. The findings were reported online June 26, 2011, in Nature. (See <a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10177.html" target="_blank">In vivo gene editing restores haemostasis in a mouse model of haemophilia</a>.)</p>
<p>Current approaches to gene therapy supply a functional version of a faulty gene without causing its integration into a chromosome, which can limit the effectiveness of the therapy; or result in integration of the new gene into a chromosome at an unpredictable location, which can be extremely dangerous.</p>
<p>The new approach delivered enzymes called <em>zinc finger nucleases</em> that cut DNA in a precise location and at the same time delivered replacement genes. The cut made by the enzymes appears to stimulate a cellular repair mechanism that swaps the replacement DNA for the existing, defective DNA, in a "cut-and-paste" maneuver.</p>
<p>In this case, the replacement DNA was for factor 9, a clotting protein, given to mice deficient in this protein because of a genetic mutation. The mice that received the combination of targeted zinc finger nucleases (ZFNs) and factor 9 genes produced enough of the clotting factor to restore nearly normal blood clotting.</p>
<p>The investigators say that the results of their "ZFN-driven gene correction" experiments raise the possibility of genome editing as a "viable strategy for the treatment of genetic disease."</p>
<p>For an article about this paper from Children's Hospital of Philadelphia, see <a href="http://www.chop.edu/news/genome-editing-corrects-hemophilia-in-animals.html" target="_blank">Genome Editing, A Next Step in Genetic Therapy, Corrects Hemophilia in Animals</a>.</p>
<h4 class="article-subhead">New approach developed for stop codon read-through</h4>
<p>Scientists at the University of Rochester (N.Y.) Medical Center have identified a new approach to <em>stop codon read-through</em>, a gene-modification technique, that could ultimately help an uncertain percentage (possibly as many as a third) of people with genetic diseases. (See <a href="http://www.nature.com/nature/journal/v474/n7351/full/nature10165.html" target="_blank">Converting nonsense codons into sense codons by targeted pseudouridylation</a> for the scientific paper; and <a href="http://www.nature.com/nature/journal/v474/n7351/full/474289a.html" target="_blank">Protein synthesis: Stop the nonsense</a> for an accompanying editorial. Both were published June 16, 2011, in Nature.)</p>
<p>For a news story about these findings from the University of Rochester Medical Center, see <a href="http://www.urmc.rochester.edu/news/story/index.cfm?id=3226" target="_blank">Changing Genetic 'Red Light' to Green Holds Promise for Treating Disease</a>.</p>
<p>Stop codon read-through is based on the idea that many cases of genetic disease are caused by <em>premature stop codons</em>, also called <em>nonsense mutations</em>, which instruct cells to stop making a protein too soon, before protein synthesis is complete. It's been estimated that up to 15 percent of people with <strong><a href="http://www.mda.org/disease/dmd.html" target="_blank">Duchenne muscular dystrophy (DMD)</a></strong> or <strong><a href="http://www.mda.org/disease/bmd.html" target="_blank">Becker muscular dystrophy (BMD)</a></strong> have the disease because of a premature stop codon in the gene for the dystrophin protein.</p>
<p>The newly developed approach to stop codon read-through alters the genetic instructions at the level of RNA, the chemical step between DNA and protein synthesis, so that a premature stop codon is no longer read as a signal to stop protein synthesis.</p>
<p>Other approaches to stop codon read-through include the experimental drug <em>ataluren</em>, in development by <a href="http://www.ptcbio.com/" target="_blank">PTC Therapeutics</a> (see <a href="http://quest.mda.org/news/low-dose-ataluren-shows-some-benefit-dmdbmd" target="_blank">Low-Dose Ataluren Shows Some Benefit in DMD/BMD</a>); and a different strategy in development by MDA grantee Carmen Bertoni at the University of California, Los Angeles (see <a href="http://quest.mda.org/news/researcher-receives-mda-grant-develop-dmd-drug" target="_blank">UCLA Researcher Receives MDA Grant to Develop DMD Drug</a>.)</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/acid-maltase-deficiency-amd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Acid Maltase Deficiency (AMD)</a></div><div class="field-item odd"><a href="/taxonomy/term/76" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Amyotrophic Lateral Sclerosis (ALS)</a></div><div class="field-item even"><a href="/disease-name/becker-muscular-dystrophy-bmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Becker Muscular Dystrophy (BMD)</a></div><div class="field-item odd"><a href="/disease-name/becker-myotonia-congenita" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Becker Myotonia Congenita</a></div><div class="field-item even"><a href="/disease-name/central-core-disease-ccd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Central Core Disease (CCD)</a></div><div class="field-item odd"><a href="/disease-name/centronuclear-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Centronuclear Myopathy</a></div><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/congenital-myasthenic-syndromes-cms" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Congenital Myasthenic Syndromes (CMS)</a></div><div class="field-item even"><a href="/disease-name/cori-disease-debrancher-enzyme-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Cori Disease (Debrancher Enzyme Deficiency)</a></div><div class="field-item odd"><a href="/disease-name/fukuyama-congenital-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Fukuyama Congenital Muscular Dystrophy</a></div><div class="field-item even"><a href="/disease-name/hauptmann-thanheuser-md-emery-dreifuss-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hauptmann-Thanheuser MD (Emery-Dreifuss Muscular Dystrophy)</a></div><div class="field-item odd"><a href="/disease-name/landouzy-dejerine-md-facioscapulohumeral-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Landouzy-Dejerine MD (Facioscapulohumeral Muscular Dystrophy)</a></div><div class="field-item even"><a href="/disease-name/mitochondrial-encephalomyopathy-lactic-acidosis-and-strokelike-episodes-melas" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes (MELAS)</a></div><div class="field-item odd"><a href="/disease-name/muscular-dystrophies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Muscular Dystrophies</a></div><div class="field-item even"><a href="/disease-name/other-myopathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Other Myopathies</a></div><div class="field-item odd"><a href="/disease-name/peripheral-neuropathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peripheral Neuropathies</a></div><div class="field-item even"><a href="/disease-name/pompe-disease-acid-maltase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Pompe Disease (Acid Maltase Deficiency)</a></div><div class="field-item odd"><a href="/disease-name/pseudohypertrophic-progressive-md-duchenne-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Pseudohypertrophic Progressive MD (Duchenne Muscular Dystrophy)</a></div><div class="field-item even"><a href="/disease-name/tarui-disease-phosphofructokinase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Tarui Disease (Phosphofructokinase Deficiency)</a></div><div class="field-item odd"><a href="/disease-name/carnitine-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Carnitine Deficiency</a></div><div class="field-item even"><a href="/disease-name/congenital-muscular-dystrophy-cmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Congenital Muscular Dystrophy (CMD)</a></div><div class="field-item odd"><a href="/disease-name/dejerine-sottas-disease-dsd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Dejerine-Sottas Disease (DSD)</a></div><div class="field-item even"><a href="/disease-name/forbes-disease-debrancher-enzyme-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Forbes Disease (Debrancher Enzyme Deficiency)</a></div><div class="field-item odd"><a href="/disease/glycogenosis-type-2" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Glycogenosis Type 2</a></div><div class="field-item even"><a href="/disease/glycogenosis-type-5" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Glycogenosis Type 5</a></div><div class="field-item odd"><a href="/disease/glycogenosis-type-10" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Glycogenosis Type 10</a></div><div class="field-item even"><a href="/disease-name/gowers-laing-distal-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Gowers-Laing Distal Myopathy</a></div><div class="field-item odd"><a href="/disease-name/integrin-deficient-congenital-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Integrin-Deficient Congenital Muscular Dystrophy</a></div><div class="field-item even"><a href="/disease-name/mitochondrial-neurogastrointestinal-encephalomyopathy-mngie" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)</a></div><div class="field-item odd"><a href="/disease-name/nemaline-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Nemaline Myopathy</a></div><div class="field-item even"><a href="/disease-name/spinal-muscular-atrophy-sma" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Spinal Muscular Atrophy (SMA)</a></div><div class="field-item odd"><a href="/disease-name/thomsen-disease-myotonia-congenita" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Thomsen Disease (Myotonia Congenita)</a></div><div class="field-item even"><a href="/disease-name/carnitine-palmityl-transferase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Carnitine Palmityl Transferase Deficiency (CPT Deficiency)</a></div><div class="field-item odd"><a href="/disease-name/distal-muscular-dystrophy-dd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Distal Muscular Dystrophy (DD)</a></div><div class="field-item even"><a href="/disease/friedreich%E2%80%99s-ataxia-fa" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Friedreich’s Ataxia (FA)</a></div><div class="field-item odd"><a href="/disease/glycogenosis-type-7" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Glycogenosis Type 7</a></div><div class="field-item even"><a href="/disease-name/mcardle-disease-phosphorylase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">McArdle Disease (Phosphorylase Deficiency)</a></div><div class="field-item odd"><a href="/disease-name/mitochondrial-dna-depletion-syndrome-mds" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Mitochondrial DNA Depletion Syndrome (MDS)</a></div><div class="field-item even"><a href="/disease-name/miyoshi-distal-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Miyoshi Distal Myopathy</a></div><div class="field-item odd"><a href="/disease-name/myotubular-myopathy-mtm-or-mm" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myotubular Myopathy (MTM or MM)</a></div><div class="field-item even"><a href="/disease-name/spinal-bulbar-muscular-atrophy-sbma" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Spinal-Bulbar Muscular Atrophy (SBMA)</a></div><div class="field-item odd"><a href="/disease-name/congenital-myotonic-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Congenital Myotonic Dystrophy</a></div><div class="field-item even"><a href="/disease-name/debrancher-enzyme-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Debrancher Enzyme Deficiency</a></div><div class="field-item odd"><a href="/disease-name/duchenne-muscular-dystrophy-dmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Duchenne Muscular Dystrophy (DMD)</a></div><div class="field-item even"><a href="/disease/glycogenosis-type-3" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Glycogenosis Type 3</a></div><div class="field-item odd"><a href="/disease/myophosphorylase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myophosphorylase Deficiency</a></div><div class="field-item even"><a href="/disease-name/myotonia-congenita-mc" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myotonia Congenita (MC)</a></div><div class="field-item odd"><a href="/disease-name/nonaka-distal-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Nonaka Distal Myopathy</a></div><div class="field-item even"><a href="/disease-name/emery-dreifuss-muscular-dystrophy-edmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Emery-Dreifuss Muscular Dystrophy (EDMD)</a></div><div class="field-item odd"><a href="/disease-name/lactate-dehydrogenase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Lactate Dehydrogenase Deficiency</a></div><div class="field-item even"><a href="/disease-name/paramyotonia-congenita" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Paramyotonia Congenita</a></div><div class="field-item odd"><a href="/disease-name/steinert-disease-myotonic-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Steinert Disease (Myotonic Muscular Dystrophy)</a></div><div class="field-item even"><a href="/disease-name/facioscapulohumeral-muscular-dystrophy-fsh-or-fshd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Facioscapulohumeral Muscular Dystrophy (FSH or FSHD)</a></div><div class="field-item odd"><a href="/disease-name/mitochondrial-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Mitochondrial Myopathy</a></div><div class="field-item even"><a href="/disease-name/periodic-paralysis" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Periodic Paralysis</a></div><div class="field-item odd"><a href="/disease-name/welander-distal-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Welander Distal Myopathy</a></div><div class="field-item even"><a href="/disease-name/limb-girdle-muscular-dystrophy-lgmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Limb-Girdle Muscular Dystrophy (LGMD)</a></div><div class="field-item odd"><a href="/disease-name/myoadenylate-deaminase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myoadenylate Deaminase Deficiency</a></div><div class="field-item even"><a href="/disease-name/muscle-eye-brain-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Muscle-Eye-Brain Disease</a></div><div class="field-item odd"><a href="/disease-name/muscular-dystrophies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Muscular Dystrophies</a></div><div class="field-item even"><a href="/disease-name/myotonic-muscular-dystrophy-mmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myotonic Muscular Dystrophy (MMD)</a></div><div class="field-item odd"><a href="/disease-name/phosphorylase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Phosphorylase Deficiency</a></div><div class="field-item even"><a href="/disease-name/kearns-sayre-syndrome-kss" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Kearns-Sayre Syndrome (KSS)</a></div><div class="field-item odd"><a href="/disease-name/metabolic-diseases-muscle" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Metabolic Diseases of Muscle</a></div><div class="field-item even"><a href="/disease-name/oculopharyngeal-muscular-dystrophy-opmd" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Oculopharyngeal Muscular Dystrophy (OPMD)</a></div><div class="field-item odd"><a href="/disease-name/phosphofructokinase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Phosphofructokinase Deficiency</a></div><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item odd"><a href="/disease-name/leigh-syndrome-and-maternally-inherited-leigh-syndrome-mils" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Leigh Syndrome and Maternally-Inherited Leigh Syndrome (MILS)</a></div><div class="field-item even"><a href="/disease-name/phosphoglycerate-kinase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Phosphoglycerate Kinase Deficiency</a></div><div class="field-item odd"><a href="/disease-name/ullrich-congenital-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Ullrich Congenital Muscular Dystrophy</a></div><div class="field-item even"><a href="/disease-name/phosphoglycerate-mutase-deficiency" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Phosphoglycerate Mutase Deficiency</a></div><div class="field-item odd"><a href="/disease-name/walker-warburg-syndrome-congenital-muscular-dystrophy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Walker-Warburg Syndrome (Congenital Muscular Dystrophy)</a></div><div class="field-item even"><a href="/disease-name/myoclonus-epilepsy-ragged-red-fibers-merrf" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Myoclonus Epilepsy with Ragged Red Fibers (MERRF)</a></div><div class="field-item odd"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/progressive-external-ophthalmoplegia-peo" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Progressive External Ophthalmoplegia (PEO)</a></div><div class="field-item odd"><a href="/disease-name/pearson-syndrome" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Pearson Syndrome</a></div><div class="field-item even"><a href="/disease-name/bethlem-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Bethlem Myopathy</a></div><div class="field-item odd"><a href="/disease-name/zasp-related-myopathy" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">ZASP-Related Myopathy</a></div><div class="field-item even"><a href="/disease-name/muscular-dystrophies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Muscular Dystrophies</a></div><div class="field-item odd"><a href="/disease-name/other-myopathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Other Myopathies</a></div><div class="field-item even"><a href="/disease-name/peripheral-neuropathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peripheral Neuropathies</a></div></div></div><div class="field field-name-field-article-link field-type-link-field field-label-above"><div class="field-label">Link:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="http://quest.mda.org/news/research-briefs-fa-mg-mm-mmd1-gene-therapy">Research Briefs: FA, MG, MM, MMD1, gene therapy</a></div></div></div><div class="field field-name-field-guid field-type-number-integer field-label-above"><div class="field-label">GUID:&nbsp;</div><div class="field-items"><div class="field-item even">19 286</div></div></div><div class="field field-name-field-quest-thumbnail-url field-type-text field-label-above"><div class="field-label">Thumbnail:&nbsp;</div><div class="field-items"><div class="field-item even">http://quest.mda.org/sites/default/files/imagecache/mda_org_frontpage100x75/man-on-globe-with-Laptop%20copy_0.jpg</div></div></div><div class="field field-name-field-article-tags field-type-taxonomy-term-reference field-label-above"><div class="field-label">Tags:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease/topic/research" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">research</a></div></div></div>Thu, 07 Jul 2011 10:28:07 +0000mdaadmindfgdg34534432257041 at http://mda.orgLiving Withhttp://mda.org/disease/charcot-marie-tooth/living-with
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><p><strong>Dear Friends:</strong></p>
<table align="right" border="0" cellpadding="8" cellspacing="0" class="photo-table" style="width: 200px;"><tbody><tr><td>
<img alt="George-Donahue" src="/sites/default/files/pictures/CMT_George-Donahue.jpg" style="float: right; width: 200px;" /></td>
</tr></tbody></table><p>I've lived with CMT since my early 20s — more than half my life. The disease has progressed slowly over the years, mostly affecting my lower legs and hands, so that now I use a manual wheelchair part time. In those years, I’ve continued a career in consumer services, hosted a local cable show educating the public about disabilities, and pursued my interests in videography and photography. I’ve also recently married, and I continue to contribute my knowledge and experience to others with disabilities.</p>
<p>These disease pages have been prepared to give you the basic knowledge about CMT that you’ll need in order to help you prepare for changes that may occur in your future. CMT is usually quite slow in progression, and while it presents challenges in daily life, there are many techniques and devices to help you adapt to those challenges.</p>
<p>You’ll read that many different genetic causes of CMT have been found, and cases vary greatly. But CMT is almost never life-threatening, and it seldom affects the heart and breathing functions.</p>
<p>And it doesn’t affect intelligence or the spirit. I know of many productive, successful people with CMT — doctors and scientists, artists and singers, athletes and teachers, active teens and students. I know children with CMT who have bright futures. We’ve all learned to strike a balance between adapting to our limitations and surroundings, and living a fulfilling life despite them.</p>
<p>I have the wonderful support of my family and great friends. I’m involved in volunteer projects that help young people with disabilities, advising them on independence and entrepreneurship, and raising public awareness about disability wherever I go. What I’ve learned — and what I try to teach — is that people with disabilities are — like everyone else — full of possibilities and gifts. These, not our limitations, are what matter.</p>
<p>Another important extended family in my life is the Muscular Dystrophy Association, which offers a great program of services, leads the world in CMT research and keeps us well informed about the disease. See the <a href="/services" target="_self">Help Through Services</a> section on this site for details of the Association’s program.</p>
<p>While MDA’s research program continues making strides toward better treatments and a cure, it’s good to know that people with disabilities have more opportunities than ever before to develop and use their abilities, and that the laws entitle us to equal employment opportunities and access to public places.</p>
<p>As you face the challenges ahead, remember, MDA and all its resources are there to help you and your family. You’re not alone.</p>
<p><strong>George J. Donahue</strong><br />
Watertown, Massachusetts</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 05:09:43 +0000mdaadmindfgdg345344329238 at http://mda.orgClinical Trialshttp://mda.org/disease/charcot-marie-tooth/clinical-trials
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><h4 class="article-subhead">
About clinical trials</h4>
<p>A clinical trial is a test in humans of an experimental medication or therapy. Clinical trials are experiments, not treatments, and participation requires careful consideration.</p>
<p>Although it's possible to benefit from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Keep your <a href="/locate" target="_self">MDA clinic</a> doctor informed about any clinical trial participation. (Note that MDA has no ability to influence who is chosen to participate in a clinical trial.)</p>
<p>For more about clinical trials in general, see <a href="http://www.clinicaltrials.gov/ct2/info/understand" target="_blank">Learn About Clinical Studies</a>, and to learn more about trial participation in neuromuscular disease, read the Quest magazine article <a href="http://quest.mda.org/article/being-co-adventurer" target="_blank">Being a Co-Adventurer</a>.</p>
<h4 class="article-subhead">
CMT clinical trials</h4>
<p>For a more refined list of CMT clinical trials, visit <a href="http://www.clinicaltrials.gov/" target="_blank">ClinicalTrials.gov</a>, a registry of federally and privately supported clinical trials in the United States and around the world. Select "Search for Clinical Trials," and follow the instructions to narrow down your search results.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 05:03:09 +0000mdaadmindfgdg345344329235 at http://mda.orgResearchhttp://mda.org/disease/charcot-marie-tooth/research
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><p>In 1991, the genetic causes of Charcot-Marie-Tooth disease (CMT) were completely unknown. By a decade later, MDA-funded scientists had helped identify 10 CMT-linked genes and found evidence for several others. (There are now thought to be more than 30 genes in which flaws can cause CMT.) This accomplishment has led to genetic testing for many types of CMT, which has greatly improved diagnosis.</p>
<p>Of equal importance, the ongoing hunt for CMT genes has given insights into treatments that might be used to stop or reverse the disorder.</p>
<p>As the CMT gene hunt continues, MDA-funded scientists are investigating how and why specific genetic mutations lead to different types of CMT. These insights are expected to lead to improved ability to predict the course of CMT in specific individuals and ultimately to treatments.</p>
<p>The current projects being pursued by MDA-supported CMT researchers include:</p>
<ul><li>
a study of calcium handling in peripheral nerve fibers;</li>
<li>
a study of the effects of CMT-causing gene mutations in zebrafish;</li>
<li>
new strategies to protect nerve fibers in mice with a disease closely resembling type 1 CMT;</li>
<li>
an exploration of the possible role of proteins called aminoacyl-tRNA synthetases in peripheral nerve diseases;</li>
<li>
an exploration of the molecular players and potential targets for therapy in a type of CMT;</li>
<li>
a study of how a loss of function in a protein called fig4 leads to type 4 CMT;</li>
<li>
an exploration of the possibility that modulators of heat shock protein 90 may be therapeutic in CMT;</li>
<li>
identification of signaling pathways that influence nerve-fiber health and injury in CMT; and</li>
<li>
a project to understand the biochemical basis of type 2A CMT by understanding the functions of the protein known as mitofusin 2.</li>
</ul><p>In addition to these specific projects, MDA is supporting the <a href="http://neurology.med.wayne.edu/neurogenetics/na_database.php" target="_blank">CMT North American Database</a>, a secure repository of information about CMT provided by patients and families. MDA also is supporting the North American CMT Network, an extension to the database designed to provide an infrastructure for CMT research.</p>
<p><a href="/disease/charcot-marie-tooth/clinical-trials" target="_self">Clinical trials in CMT</a> also are under way.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item odd"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item even"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:56:24 +0000mdaadmindfgdg345344329234 at http://mda.orgMedical Managementhttp://mda.org/disease/charcot-marie-tooth/medical-management
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><p>Although there’s no cure for CMT, there are treatments that can be used to effectively manage its symptoms. These treatments have allowed many people with the disease to lead active, productive lives.</p>
<p><strong><a id="top" name="top"></a>This section addresses the following:</strong></p>
<table width="100%"><tbody><tr><td colwidth="50%" style="width: 491px;">
<p><a href="#breathing" target="_self">Breathing difficulties</a><br /><a href="#drugs" target="_self">Drug warning</a><br /><a href="#hand_weakness" target="_self">Hand weakness</a></p>
</td>
<td colwidth="50%" style="width: 481px;">
<p><a href="#leg-ankle-foot" target="_self">Leg, ankle and foot difficulties</a><br /><a href="#mobility" target="_self">Mobility difficulties</a><br /><a href="#sensory_loss" target="_self">Sensory loss</a></p>
</td>
</tr></tbody></table><hr /><h4 class="article-subhead"><a id="breathing" name="breathing"></a>Breathing difficulties</h4>
<p>Weakness of the respiratory muscles is rare in people with CMT, but when it occurs it can be life-threatening. If you regularly experience shortness of breath, you should have your breathing checked by a specialist, who might recommend occasional or nighttime use of a device that delivers air under pressure into the lungs.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><strong><a id="drugs" name="drugs"></a></strong>Drug warning</h4>
<p>The use of certain prescription drugs or excess alcohol can lead to acquired neuropathy, and thus might exacerbate CMT. Case studies have shown that the chemotherapy drug vincristine can cause rapid deterioration in people with CMT.</p>
<p>When taking a prescription drug for the first time, it’s a good idea to consult your doctor about its possible effects on CMT. Or, enter the specific name of the drug into an Internet search engine, along with the words “prescribing information,” to receive a full explanation of what the drug does and what its side effects may be.</p>
<p>You’re unlikely to see anything specific about CMT. However, if the medication’s side effect description mentions words like <em>neuropathy</em>, <em>paresthesias</em>, <em>neuropathic pain</em> or <em>peripheral nerve damage</em>, you may want to consult your physician about its use in CMT and possible alternatives.</p>
<p>Lists of contraindicated (forbidden) drugs for people with CMT are often composed mostly of medications used to treat serious conditions, such as cancer. In these cases, there may be no alternative to taking the drug, with the awareness that CMT symptoms may worsen.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="hand_weakness" name="hand_weakness"></a>Hand weakness</h4>
<p>Late in the course of CMT, many people experience weakness in the hands and forearms, and have difficulty with gripping and fine finger movements, such as turning doorknobs, and buttoning and zippering clothes. Often, these problems can be overcome with occupational therapy, which helps people accomplish the “job” of daily living through the use of assistive devices.</p>
<p>For example, an occupational therapist might recommend that you put special rubber grips on your home’s doors, or buy clothes that fasten with Velcro or snaps. Your <a href="/locate" target="_self">MDA clinic</a> can refer you to an occupational therapist.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="leg-ankle-foot" name="leg-ankle-foot"></a>Leg, ankle and foot difficulties</h4>
<table class="photo-table" style="width: 200px;" border="0" cellpadding="8" cellspacing="0" align="right"><tbody><tr><td><img alt="Ankle-foot orthosis" src="/sites/default/files/pictures/leg_braces.jpg" style="width: 200px;" /></td>
</tr><tr><td>An ankle-foot orthosis fits snugly around the foot and ankle.</td>
</tr></tbody></table><p>Many people with CMT make their first visit to a neurologist after they notice frequent trips and falls, ankle sprains, or ankle fractures, caused by foot drop. When these problems occur, some people find they can overcome them just by wearing boots or high-top shoes to support the ankles.</p>
<p>Others might require leg braces, such as an <a href="http://quest.mda.org/article/putting-your-best-foot-forward" target="_blank">ankle-foot orthosis (AFO)</a>, a removable cast that fits snuggly around the foot and ankle. Once made of clunky metal struts that required special shoes, AFOs are now made of lightweight plastic that’s custom-molded to fit the wearer’s legs, and can be worn underneath pants and tennis shoes.</p>
<p>Foot contractures also can be delayed by using AFOs, which force the feet into a normal position and decrease stress on the ankles. Similarly, splints can be used to prevent unintended flexing of the toes.</p>
<p>If these methods fail and severe contractures occur, surgery can be used to loosen up tight muscles and tendons, or to correct bone deformities.</p>
<p>One of the most effective ways to keep muscles from tightening up and forming contractures is to begin a regular program of physical therapy, which usually consists of low-impact exercises and stretching.</p>
<p>Your <a href="/locate">MDA clinic</a> can help get you started on an individualized physical therapy program.</p>
<p>For more on medical management of CMT, see <a href="http://quest.mda.org/article/surgery-sometimes-bracing-often-caution-always" target="_blank">Surgery Sometimes, Bracing Often, Caution Always: Caring for the CMT-affected foot</a>.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="mobility" name="mobility"></a>Mobility difficulties</h4>
<p>Many people with CMT won’t need a wheelchair or motorized scooter, but an older person with advanced CMT or someone with a severe type might require one of these to get around, especially when traversing long distances. Like AFOs, wheelchairs aren’t what they used to be. There are wheelchairs that can be used on almost any terrain — from shopping mall to hiking trail — many of them powered by the flip of a switch.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="sensory_loss" name="sensory_loss"></a>Sensory loss</h4>
<p>Combined with the regular abrasions caused by <a href="/disease/charcot-marie-tooth/signs-and-symptoms#contractures" target="_self">foot deformities</a>, the lack of pain sensitivity makes people with CMT at risk for developing ulcerations — wounds that have gone unnoticed and become severely infected. If you have CMT, and especially if you have any foot deformities, you should check your feet regularly for injuries.</p>
<p>Paradoxically, despite sensory loss, some people with CMT experience pain — a combination of painful muscle cramps and neuropathic pain. This pain isn’t caused by an external trigger but by defective signals in sensory axons. Both types of pain usually can be alleviated with medication.</p>
<p>In many people with CMT, sensory loss is associated with dry skin and hair loss in the affected area.</p>
<p>In rare cases, sensory loss can include gradual hearing impairment and sometimes deafness. Watching out for these potential problems will enable you to seek appropriate treatment if necessary.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:53:26 +0000mdaadmindfgdg345344329233 at http://mda.orgCauses/Inheritancehttp://mda.org/disease/charcot-marie-tooth/causes-inheritance
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><h4 class="article-subhead">
Causes of Charcot-Marie-Tooth disease (CMT)</h4>
<table align="right" border="0" cellpadding="8" cellspacing="0" class="photo-table" style="width: 300px;"><tbody><tr><td>
<img alt="peripheral nerve fibers" src="/sites/default/files/pictures/CMT_2.jpg" style="width: 350px; height: 406px;" /></td>
</tr><tr><td>
<p>Peripheral nerves control movement by relaying impulses from the spinal cord (not shown) to the muscles (shown in the forearm). They also convey sensation and help with balance and awareness of the body’s position.</p>
<p>A single movement-controlling peripheral nerve is composed of many long nerve cell branches — called axons — that extend from the spinal cord and connect to muscle fibers. Each axon is surrounded by myelin made from the wrappings of Schwann cells.</p>
</td>
</tr></tbody></table><p>CMT damages the peripheral nerves, which connect the spinal cord with the rest of the body. The peripheral nerve fibers, called <em>axons</em>, extend from sensory nerve cells in the body's periphery back toward the spinal cord, and from muscle-controlling nerve cells in the spinal cord out toward the muscles. Axons transmit electrical signals for sensation and movement to and from the spinal cord.</p>
<p>More than 30 genes have been implicated in Charcot-Marie-Tooth disease (CMT).</p>
<p>In different types of CMT, peripheral nerve damage can be caused by defects in genes coding for proteins affecting axons, or by defects in genes coding for proteins affecting the insulating <em>myelin</em> coating around each axon — or both.</p>
<p>In order for a person to move and react with precision and speed, axons have to transmit their signals within a fraction of a second. This is a real challenge for axons that have to stretch over long distances, like the ones connected to muscles in fingers and toes.</p>
<p>The longest axons in the body are especially sensitive to damage, which explains why CMT mostly causes motor and sensory problems in the body’s extremities.</p>
<h4 class="article-subhead">
Inheritance patterns in CMT</h4>
<p>Although CMT can look very similar to an acquired neuropathy — a type of nerve damage caused by diabetes, immunological abnormalities or exposure to certain chemicals or drugs — it isn’t caused by anything a person does, and it isn’t contagious. It’s hereditary, meaning that it can be passed down through a family from one generation to the next.</p>
<p>Because of these features, CMT is sometimes called hereditary motor and sensory neuropathy (HMSN). Some doctors also use the old-fashioned name peroneal muscular atrophy, which refers to atrophy of the peroneal muscle in the lower leg.</p>
<p>CMT can run in a family, even when there’s no obvious family history. In part, this is because CMT can be inherited in three different ways that aren’t always easy to trace through a family tree: X-linked, autosomal dominant and autosomal recessive.</p>
<p>X-linked means that the genetic defect (or mutation) is located on the X chromosome. In females, who have two X chromosomes, a normal copy of the gene on one chromosome can often compensate (at least partially) for the defective copy. Therefore, X-linked diseases usually affect males more severely than females, because males only have one X chromosome. X-linked diseases (like <a href="/disease/charcot-marie-tooth/cmtx" target="_self">CMTX</a>) can’t be passed from father to son.</p>
<p>Autosomal means the mutation occurs on a chromosome other than the X or Y. Therefore, autosomal diseases affect males and females equally. Autosomal recessive means that two copies of a defective gene are required for the full-blown disease. One copy is inherited from each parent, neither of whom would normally have the disease. Autosomal dominant means one copy of a defective gene is enough to cause disease. A person who inherits the defective gene from a parent will have the disease, as will the parent.</p>
<p>When CMT is passed on in an autosomal dominant pattern, it can be easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types of CMT might seem to occur “out of the blue.” But in reality, the mother or both parents might be <em>carriers</em> who silently harbor a genetic mutation. Many parents have no idea they’re carriers of a disease until they have a child with the disease.</p>
<p>CMT also can occur when a new mutation occurs during the child’s conception. These are called <em>spontaneous mutations</em>, and after they occur, they can be passed on to the next generation.</p>
<p>Your risk of inheriting or passing on CMT depends largely on what <a href="/disease/charcot-marie-tooth/types-cmt" target="_self">type of CMT you have</a>.</p>
<p>A good way to find out more about this risk is to talk with your <a href="/locate" target="_self">MDA clinic</a> physician or a genetic counselor at the MDA clinic. Also, see <a href="/publications/facts-about-genetics-and-NMDs" target="_self">Facts About Genetics and Neuromuscular Diseases</a>.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:31:04 +0000mdaadmindfgdg345344329231 at http://mda.orgDiagnosishttp://mda.org/disease/charcot-marie-tooth/diagnosis
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><p>A combination of lower leg weakness and foot deformities is a red flag for Charcot-Marie-Tooth disease (CMT) but isn’t sufficient for diagnosis. When a patient has those symptoms, a neurologist will usually start with a physical exam to look for further signs of distal weakness and sensory loss.</p>
<p>As a test for leg weakness, a neurologist might ask patients to walk on their heels or move part of their leg against an opposing force.</p>
<p>To look for sensory loss, the neurologist will usually test the patient’s deep tendon reflexes (like the knee-jerk reflex), which are reduced or absent in most people with CMT.</p>
<p>During this initial evaluation, the neurologist also will ask about the patient’s family history. A family history of CMT-like symptoms, combined with signs of nerve damage from the individual’s physical exam, strongly point to CMT or another hereditary neuropathy.</p>
<p>Lack of a family history doesn’t rule out CMT, but might prompt the neurologist to ask about diabetes, overexposure to certain drugs and other potential causes of neuropathy.</p>
<p>Next, if the diagnosis is still consistent with CMT, the neurologist may arrange for genetic testing. These tests, done by drawing a blood sample, are designed to detect the most common genetic defects known to cause CMT. Many, but certainly not all, of the genetic mutations underlying CMT can be detected with a DNA blood test. For more on getting a definitive genetic diagnosis, see <a class="ext" href="http://quest.mda.org/article/genetic-testing-21st-century" target="_blank">The Genie's Out of the Bottle: Genetic testing in the 21st century</a>.</p>
<p>A positive genetic test result can provide a definite diagnosis and useful information for family planning. But once again, a negative result doesn’t rule out CMT.</p>
<p>The neurologist also may perform a <a href="http://quest.mda.org/article/simply-stated-EMGs-and-NCV-tests" target="_blank"><em>nerve conduction velocity (NCV)</em> test</a>, which measures the strength and speed of electrical signals transmitted through nerves. It’s done by placing surface electrodes, similar to those used for electrocardiograms, on the skin at various points over a nerve. One electrode delivers a mild shock that stimulates an electrical response in the nerve, and the others record this response as it travels through the nerve.</p>
<p>Delayed responses are a sign of <em>demyelination</em> and small responses are a sign of axonopathy. Thus, NCV is often used to distinguish between <a href="/disease/charcot-marie-tooth/cmt1-cmt2" target="_self">CMT1 and CMT2</a>.</p>
<p>Other procedures sometimes used to diagnose CMT include <a href="http://quest.mda.org/article/simply-stated-EMGs-and-NCV-tests" target="_blank"><em>electromyography </em>(EMG)</a>, which measures the electrical signals in muscles, and less commonly, <em>nerve biopsy</em>, which involves the removal and examination of a small piece of nerve.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/peripheral-neuropathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peripheral Neuropathies</a></div><div class="field-item odd"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item odd"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:29:26 +0000mdaadmindfgdg345344329230 at http://mda.orgSigns and Symptomshttp://mda.org/disease/charcot-marie-tooth/signs-and-symptoms
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><p>Partly because there are <a href="/disease/charcot-marie-tooth/types-cmt">different types of Charcot-Marie-Tooth disease (CMT)</a>, the exact symptoms vary greatly from person to person. This section presents a general picture of CMT signs and symptoms.</p>
<p><strong><a id="top" name="top"></a>This section covers:</strong></p>
<ul><li><a href="#contractures" target="_self">Contractures and bone deformities</a></li>
<li><a href="#muscle_weakness" target="_self">Muscle weakness</a></li>
<li><a href="#sensory_loss" target="_self">Sensory loss</a></li>
</ul><hr /><h4 class="article-subhead"><a id="contractures" name="contractures"></a>Contractures and bone deformities</h4>
<table class="photo-table" style="width: 200px; height: 169px;" border="0" cellpadding="8" cellspacing="0" align="right"><tbody><tr><td><img alt="Feet with high arches are common in CMT" src="/sites/default/files/pictures/foot-side.jpg" style="width: 200px;" /></td>
</tr><tr><td>Foot contractures resulting in high-arched feet often occur in CMT.</td>
</tr><tr><td><img alt="Example of a hand contracture in a person with CMT" src="/sites/default/files/pictures/CMT_hand.jpg" style="width: 200px;" /></td>
</tr><tr><td>Hand contractures can occur late in the course of CMT.</td>
</tr></tbody></table><p>Many people with CMT eventually develop contractures (stiffened joints) that result in deformities of the feet and hands.</p>
<p>The contractures occur because as some muscles around a joint weaken, others remain strong, contracting and pulling on the joint. Over time, the bones around the joint shift into abnormal positions.</p>
<p>For example, as muscles that lift the foot at the ankle become weak, muscles that lower and curl the foot downward contract and tighten, causing the most common type of foot deformity — a shortened foot with a high arch (pes cavus). As the contracture gets worse, the toes can become locked in a flexed position.</p>
<p>A small fraction of people with CMT develop “flat feet” (pes planus), presumably because of a different pattern of muscle weakness.</p>
<p>During walking, these deformities can cause unusual friction against the toes, heel and ball of the foot, leading to painful abrasions, blisters and calluses.</p>
<p>If left untreated, the contractures and secondary abrasions tend to worsen over time, making it increasingly difficult to walk.</p>
<p>As CMT progresses, contractures in the hand can lock the fingers in a flexed position, and in rare cases, severe proximal weakness can lead to scoliosis (side-to-side curvature of the spine) or kyphosis (front-to-back spine curvature).</p>
<p>A small fraction of people with severe CMT also experience hip displacement at an early age.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="muscle_weakness" name="muscle_weakness"></a>Muscle weakness</h4>
<p>In general, people with CMT experience slowly progressive weakness and wasting in the distal muscles, the muscles furthest from the center of the body.</p>
<p>The muscles that control the feet, lower legs, forearms and hands are most affected.</p>
<table class="photo-table" style="width: 200px; height: 200px;" border="0" cellpadding="8" cellspacing="0" align="right"><tbody><tr><td><img alt="Example of foot drop in a person with CMT" src="/sites/default/files/pictures/foot-measure.jpg" style="width: 200px; height: 118px;" /></td>
</tr><tr><td>People with CMT frequently have foot drop — difficulty lifting the foot at the ankle.</td>
</tr></tbody></table><p>The proximal muscles, which are those closer to the center of the body, such as the upper arm and upper leg muscles, are rarely affected.</p>
<p>Usually, weakness begins in the feet and ankles, and manifests itself as foot drop — difficulty lifting the foot at the ankle, so that the toes point downward during walking.</p>
<p>Foot drop causes frequent tripping, and with increasing weakness and attempts at compensation, the affected person develops an abnormal gait.</p>
<p>Although it’s usually too slight to cause disability or discomfort, some people with CMT experience tremor (involuntary shaking).</p>
<p>CMT with obvious tremor is sometimes called Roussy-Levy syndrome.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
<h4 class="article-subhead"><a id="sensory_loss" name="sensory_loss"></a>Sensory loss</h4>
<p>Because CMT causes damage to sensory nerve fibers (axons), there can be tingling and burning sensations in the hands and feet, usually causing only mild discomfort but sometimes causing pain. The sense of touch is diminished, as is the ability to sense changes in temperature.</p>
<p>Even though they may have sensory loss, many people with CMT experience cold hands and feet, which may be related to loss of insulating muscle in these areas.</p>
<p>People may sustain injuries to the hands and feet without realizing it, so they should check regularly for such injuries to avoid infection.</p>
<p>In many people with CMT, sensory loss is associated with dry skin and hair loss in the affected area.</p>
<p>In rare cases, sensory loss can include gradual hearing impairment and sometimes deafness.</p>
<p style="text-align: right;"><a href="#top" target="_self">Back to top</a></p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item odd"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item even"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:23:36 +0000mdaadmindfgdg345344329229 at http://mda.orgDejerine-Sottas diseasehttp://mda.org/disease/charcot-marie-tooth/dejerine-sottas
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><h4 class="article-subhead">
What is Dejerine-Sottas disease?</h4>
<p>Dejerene-Sottas (DS) is a subtype of Charcot-Marie-Tooth disease (CMT), a genetic, neurological disorder that causes damage to the peripheral nerves — tracts of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs. DS is named for Joseph Dejerine and Jules Sottas, French neurologists who first described the disorder in 1893.</p>
<p>DS is sometimes classified as a subgroup of <a href="/disease/charcot-marie-tooth/cmt4">CMT4</a>, and also is sometimes called type 3 hereditary motor and sensory neuropathy or HMSN3.</p>
<h4 class="article-subhead">
What are the symptoms of DS?</h4>
<p>DS is a severe neuropathy (disease or abnormality of the nerves), with generalized weakness sometimes progressing to profound disability, loss of or changes in sensation, curvature of the spine and sometimes mild hearing loss. For more, see <a href="/disease/charcot-marie-tooth/signs-and-symptoms" target="_self">Signs and Symptoms</a>.</p>
<h4 class="article-subhead">
What causes DS?</h4>
<p>DS is caused by defects in the genes for proteins found in axons, fibers that carry electrical signals between the brain and spinal cord and the rest of the body, or in the genes for proteins found in myelin, a coating on axons that insulates and nourishes them.</p>
<p>DS is inherited in an autosomal dominant or recessive pattern. For more, see <a href="/disease/charcot-marie-tooth/causes-inheritance" target="_self">Causes/Inheritance</a>.</p>
<h4 class="article-subhead">
What is the progression of DS?</h4>
<p>DS begins in infancy or early childhood, and progresses slowly. Severe disability may eventually occur.</p>
<h4 class="article-subhead">
What is the status of research on DS?</h4>
<p><a href="/disease/charcot-marie-tooth/research" target="_self">DS research</a> is focused on exploring the effects of defects in genes related to the peripheral nervous system and devising strategies to combat these effects.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/peripheral-neuropathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peripheral Neuropathies</a></div><div class="field-item odd"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item odd"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:12:54 +0000mdaadmindfgdg345344329227 at http://mda.orgCMT4http://mda.org/disease/charcot-marie-tooth/cmt4
<div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><h4 class="article-subhead">
What is Charcot-Marie-Tooth disease type 4 (CMT4)?</h4>
<p>CMT4 is a subtype of CMT, a genetic, neurological disorder that causes damage to the peripheral nerves — tracts of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs.</p>
<h4 class="article-subhead">
What are the symptoms of CMT4?</h4>
<p>CMT4 causes weakness, usually mostly distal (far from the center of the body) but sometimes involving proximal (near the center of the body) muscles. Impairment or changes in sensations (such as the sense of touch or ability to perceive temperature changes) also can occur. When CMT4 begins in infancy, it’s characterized by low muscle tone. See <a href="/disease/charcot-marie-tooth/signs-and-symptoms" target="_self">Signs and Symptoms</a> for more.</p>
<h4 class="article-subhead">
What causes CMT4?</h4>
<p>CMT4 is caused by defects in the genes that affect myelin, a coating that insulates and nourishes axons (fibers that carry electrical signals between the brain and spinal cord and the rest of the body).</p>
<p>CMT4 is inherited in an autosomal recessive pattern. For more, see <a href="/disease/charcot-marie-tooth/causes-inheritance" target="_self">Causes/Inheritance</a>.</p>
<h4 class="article-subhead">
What is the progression of CMT4?</h4>
<p>CMT4 has its onset in infancy, childhood or adolescence, and progression is generally slow. Young children with CMT4 can have delayed motor (movement-related) development.</p>
<h4 class="article-subhead">
What is the status of research on CMT?</h4>
<p><a href="/disease/charcot-marie-tooth/research" target="_self">CMT research</a> is focused on exploring the effects of defects in genes related to the peripheral nervous system and devising strategies to combat these effects.</p>
</div></div></div><div class="field field-name-field-article-disease field-type-taxonomy-term-reference field-label-above"><div class="field-label">Disease:&nbsp;</div><div class="field-items"><div class="field-item even"><a href="/disease-name/peripheral-neuropathies" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peripheral Neuropathies</a></div><div class="field-item odd"><a href="/disease-name/charcot-marie-tooth-disease-cmt" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Charcot-Marie-Tooth Disease (CMT)</a></div><div class="field-item even"><a href="/disease-name/hereditary-motor-and-sensory-neuropathy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)</a></div><div class="field-item odd"><a href="/disease-name/peroneal-muscular-atrophy-charcot-marie-tooth-disease" typeof="skos:Concept" property="rdfs:label skos:prefLabel" datatype="">Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)</a></div></div></div>Thu, 23 Jun 2011 04:10:47 +0000mdaadmindfgdg345344329226 at http://mda.org